Figure 5. Examples of intergenerational epigenetic inheritance in vertebrate model systems.

(A) Paternal protein restriction has been reported to cause intergenerational inheritance of metabolic symptoms in F1 offspring, despite being restored to normal nutrition postnatally. Analysis of liver tissue in F1 offspring of protein-restricted fathers showed altered DNA methylation and gene expression changes, which may contribute to the phenotype. No altered methylation was detected in the sperm of protein-restricted fathers, however. (B) Maternal caloric restriction causes metabolic dysfunction, reduced lifespan and fertility in offspring up to the F2 generation. Analysis of sperm in F1 offspring revealed methylation and gene expression changes which may be linked to the phenotype. Gene expression changes were also observed in the brains and livers of F2 offspring, but no methylation changes were observed. Red circles represent altered gene expression, and blue circles represent wild-type levels of gene expression. Figure references: [42,45,62,64].